OBJECTIVES: The objectives are to use the isomeric cyclopentanetriols which are formal analogs of glycerol to study the relationship of the rotational state of the backbone of glycerolipids to physical and biological properties. The synthetic methods for the cyclitols and the analogs were developed and the conformations were determined in this laboratory. Specific problems include: 1. Synthesis of analogs of glycerolipids. Tri-, di- and monoglyceride analogs; phosphatidic acids, phosphatidyl ethanolamine, phosphatidyl choline, phosphatidylserine; analogs of biosynthetic intermediates, in which glycerol is replaced by each of the cyclopentane-1,2,3-triols. Populated conformational states of the isomers correspond to many possible rotamers of glycerol. 2. Physical studies of lipid analogs. The relationship of configuration of the backbone to physical properties will be studied. 2H and 13C nuclear magnetic resonance, electron paramagnetic resonance involving spin-labels, Raman spectroscopy, dfferential scanning calorimetry, force-area curves in monolayers, etc. will be applied to the analogs in bulk, in bilamellar and in multilamellar dispersions. 3. Biological studies of lipid analogs. The analogs wll be tested as substrates or inhibitors of lipid-metabolizing enzymes, e.g., enzymes synthesizing phosphatidyl serine, phosphatidyl glycerol phosphate, phosphatidyl ethanolamine; various lipases, esterases and phospholipases. It will be determined whether any of the analogs are advantageous for preparing liposomes for packaging of enzymes. Reconstitution of lipoproteins from analogs and apolipoproteins will be investigated. In addition, the ability of various of the analogs to affect processes related to experimental atherogenesis in cell culture will be investigated.